RESUMO
BACKGROUND: We previously reported excellent three-year overall survival (OS) for patients with newly diagnosed intermediate-risk neuroblastoma treated with a biology- and response-based algorithm on the Children's Oncology Group study ANBL0531. We now present the long-term follow-up results. METHODS: All patients who met the age, stage, and tumor biology criteria for intermediate-risk neuroblastoma were eligible. Treatment was based on prognostic biomarkers and overall response. Event-free survival (EFS) and OS were estimated by the Kaplan-Meier method. RESULTS: The 10-year EFS and OS for the entire study cohort (n = 404) were 82.0% (95% confidence interval (CI), 77.2%-86.9%) and 94.7% (95% CI, 91.8%-97.5%), respectively. International Neuroblastoma Staging System stage 4 patients (n = 133) had inferior OS compared with non-stage 4 patients (n = 271; 10-year OS: 90.8% [95% CI, 84.5%-97.0%] vs 96.6% [95% CI, 93.9%-99.4%], p = .02). Infants with stage 4 tumors with ≥1 unfavorable biological feature (n = 47) had inferior EFS compared with those with favorable biology (n = 61; 10-year EFS: 66.8% [95% CI, 50.4%-83.3%] vs 86.9% [95% CI, 76.0%-97.8%], p = .02); OS did not differ (10-year OS: 84.4% [95% CI, 71.8%-97.0%] vs 95.0% [95% CI, 87.7%-100.0%], p = .08). Inferior EFS but not OS was observed among patients with tumors with (n = 26) versus without (n = 314) 11q loss of heterozygosity (10-year EFS: 68.4% [95% CI, 44.5%-92.2%] vs 83.9% [95% CI, 78.7%-89.2%], p = .03; 10-year OS: 88.0% [95% CI, 72.0%-100.0%] vs 95.7% [95% CI, 92.8%-98.6%], p = .09). CONCLUSIONS: The ANBL0531 trial treatment algorithm resulted in excellent long-term survival. More effective treatments are needed for subsets of patients with unfavorable biology tumors.
Assuntos
Neuroblastoma , Humanos , Neuroblastoma/mortalidade , Neuroblastoma/terapia , Neuroblastoma/patologia , Masculino , Feminino , Seguimentos , Pré-Escolar , Lactente , Criança , Taxa de Sobrevida , Prognóstico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recém-Nascido , Estadiamento de NeoplasiasRESUMO
PURPOSE: The primary objective of the Children's Oncology Group study ANBL0531 (ClinicalTrials.gov identifier: NCT00499616) was to reduce therapy for subsets of patients with intermediate-risk neuroblastoma using a biology- and response-based algorithm to assign treatment duration while maintaining a 3-year overall survival (OS) of 95% or more for the entire cohort. PATIENTS AND METHODS: Children younger than age 12 years with intermediate-risk stage 2A/2B or stage 3 tumors with favorable histology; infants younger than age 365 days with stage 3, 4 or 4S disease; and toddlers from 365 to younger than 547 days with favorable histology, hyperdiploid stage 4, or unfavorable histology stage 3 tumors were eligible. Patients with MYCN-amplified tumors were excluded. Patients were assigned to initially receive two (group 2), four (group 3), or eight (group 4) cycles of chemotherapy with or without surgery on the basis of prognostic markers, including allelic status of chromosomes 1p and 11q; ultimate duration of therapy was determined by overall response. RESULTS: Between 2007 and 2011, 404 evaluable patients were enrolled. Compared with legacy Children's Oncology Group studies, subsets of patients had a reduction in treatment. The 3-year event-free survival and OS rates were 83.2% (95% CI, 79.4% to 87.0%) and 94.9% (95% CI, 92.7% to 97.2%), respectively. Infants with stage 4 tumors with favorable biology (n = 61) had superior 3-year event-free survival compared with patients with one or more unfavorable biologic features (n = 47; 86.9% [95% CI, 78.3% to 95.4%] v 66.8% [95% CI, 53.1% to 80.6%]; P = .02), with a trend toward OS advantage (95.0% [95% CI, 89.5% to 100%] v 86.7% [95% CI, 76.6% to 96.7%], respectively; P = .08). OS for patients with localized disease was 100%. CONCLUSION: Excellent survival was achieved with this treatment algorithm, with reduction of therapy for subsets of patients. More-effective treatment strategies still are needed for infants with unfavorable biology stage 4 disease.
Assuntos
Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Técnicas de Apoio para a Decisão , Terapia Neoadjuvante , Neuroblastoma/terapia , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Tomada de Decisão Clínica , Esquema de Medicação , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Estadiamento de Neoplasias , Neuroblastoma/genética , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Intervalo Livre de Progressão , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados UnidosRESUMO
PURPOSE: Infants with stage 4S neuroblastoma usually have favorable outcomes with observation or minimal chemotherapy. However, young infants with symptoms secondary to massive hepatomegaly or with unfavorable tumor biology are at high risk of death. Our aim was to improve outcomes for patients with symptomatic and/or unfavorable biology 4S neuroblastoma with a uniform treatment approach using a biology- and response-based algorithm. PATIENTS AND METHODS: The subset of patients with 4S disease with MYCN-not amplified tumors with impaired or impending organ dysfunction, or with unfavorable histology and/or diploid DNA index, were eligible. Patients were assigned to receive two, four, or eight cycles of chemotherapy on the basis of histology, diploid DNA index, chromosome arm 1p or 11q loss of heterozygosity (LOH) status, and symptoms. RESULTS: Forty-nine eligible patients were enrolled: 41 were symptomatic and 28 had unfavorable biology. Seventeen patients (symptomatic, favorable biology) were assigned two cycles, 21 patients (any unfavorable biologic feature without 1p or 11q LOH) were assigned four cycles, and 11 patients (unfavorable biology including 1p and/or 11q LOH [n = 7] or symptomatic with unknown biology [n = 4]), were assigned eight cycles. The 3-year overall survival was 81.4% ± 5.8%. Eight of nine deaths were in patients younger than 2 months of age at diagnosis (median, 9 days [range, 1 to 68 days]): five acute deaths were a result of hepatomegaly and associated toxicities; two were a result of late relapse in patients with unfavorable biology; and two were a result of treatment complications. No deaths occurred after protocol-mandated pre-emptive treatment of infants younger than 2 months with hepatomegaly, regardless of symptoms. A new scoring algorithm for emergent chemotherapy in patients with 4S disease was developed on the basis of this experience. CONCLUSION: The outcome for 4S neuroblastoma can be improved with pre-emptive chemotherapy for evolving hepatomegaly or other baseline comorbidities in infants younger than 2 months of age.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neuroblastoma/diagnóstico , Neuroblastoma/tratamento farmacológico , Carboplatina/administração & dosagem , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Filgrastim/administração & dosagem , Amplificação de Genes , Hepatomegalia/patologia , Hepatomegalia/terapia , Humanos , Lactente , Recém-Nascido , Perda de Heterozigosidade , Masculino , Proteína Proto-Oncogênica N-Myc/genética , Estadiamento de Neoplasias , Neuroblastoma/genética , Neuroblastoma/patologia , Fatores de Risco , Taxa de SobrevidaRESUMO
UNLABELLED: PURPOSE We assessed the long-term outcome of patients enrolled on CCG-3891, a high-risk neuroblastoma study in which patients were randomly assigned to undergo autologous purged bone marrow transplantation (ABMT) or to receive chemotherapy, and subsequent treatment with 13-cis-retinoic acid (cis-RA). PATIENTS AND METHODS Patients received the same induction chemotherapy, with random assignment (N = 379) to consolidation with myeloablative chemotherapy, total-body irradiation, and ABMT versus three cycles of intensive chemotherapy. Patients who completed consolidation without disease progression were randomly assigned to receive no further therapy or cis-RA for 6 months. Results The event-free survival (EFS) for patients randomly assigned to ABMT was significantly higher than those randomly assigned to chemotherapy; the 5-year EFS (mean +/- SE) was 30% +/- 4% versus 19% +/- 3%, respectively (P = .04). The 5-year EFS (42% +/- 5% v 31% +/- 5%) from the time of second random assignment was higher for cis-RA than for no further therapy, though it was not significant. Overall survival (OS) was significantly higher for each random assignment by a test of the log(-log(.)) transformation of the survival estimates at 5 years (P < .01). The 5-year OS from the second random assignment of patients who underwent both random assignments and who were assigned to ABMT/cis-RA was 59% +/- 8%; for ABMT/no cis-RA, it was 41% +/- 8% [corrected]; for continuing chemotherapy/cis-RA, it was 38% +/- 7%; and for chemotherapy/no cis-RA, it was 36% +/- 7%. CONCLUSION: Myeloablative therapy and autologous hematopoietic cell rescue result in significantly better 5-year EFS than nonmyeloablative chemo therapy; neither myeloablative therapy with [corrected] autologous hematopoietic cell rescue nor cis-RA given after consolidation therapy significantly improved OS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Isotretinoína/uso terapêutico , Neuroblastoma/terapia , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Humanos , Lactente , Neuroblastoma/patologia , Análise de Sobrevida , Irradiação Corporal TotalRESUMO
BACKGROUND: The components of therapy required for patients with INSS Stage 3 neuroblastoma and high-risk features remain controversial. PROCEDURE: A retrospective cohort design was used to determine if intensive chemoradiotherapy with purged autologous bone marrow rescue (ABMT) and/or 13-cis-retinoic acid (13-cis-RA) improved outcome for patients with high-risk neuroblastoma that was not metastatic to distant sites. We identified 72 patients with INSS Stage 3 neuroblastoma enrolled between 1991 and 1996 on the Phase 3 CCG-3891 randomized trial. Patients were analyzed on an intent-to-treat basis using a log-rank test. RESULTS: The 5-year event-free survival (EFS) and overall survival (OS) rates for patients with Stage 3 neuroblastoma were 55 +/- 6% and 59 +/- 6%, respectively (n = 72). Patients randomized to ABMT (n = 20) had 5-year EFS of 65 +/- 11% and OS of 65 +/- 11% compared to 41 +/- 11 (P = 0.21) and 46 +/- 11% (P = 0.23) for patients randomized to CC (n = 23), respectively. Patients randomized to 13-cis-RA (n = 23) had 5-year EFS of 70 +/- 10% and OS of 78 +/- 9% compared to 63 +/- 12% (P = 0.67) and 67 +/- 12% (P = 0.55) for those receiving no further therapy (n = 16), respectively. Patients randomized to both ABMT and 13-cis-RA (n = 6) had a 5-year EFS of 80 +/- 11% and OS of 100%. CONCLUSION: Patients with high-risk Stage 3 neuroblastoma have an overall poor prognosis despite aggressive chemoradiotherapy. Further studies are warranted to determine if myeloablative consolidation followed by 13-cis-RA maintenance therapy statistically significantly improves outcome.
Assuntos
Transplante de Medula Óssea/métodos , Isotretinoína/uso terapêutico , Neuroblastoma/terapia , Purging da Medula Óssea , Cisplatino , Terapia Combinada , Ciclofosfamida , Doxorrubicina , Etoposídeo , Humanos , Lactente , Neuroblastoma/mortalidade , Radioterapia , Risco , Análise de Sobrevida , Transplante Autólogo , Resultado do TratamentoRESUMO
We recently revised a redundant colon conduit in a boy who was born with isolated esophageal atresia. In view of the paucity of reports dealing with correction of this common complication of esophageal replacement, it seemed appropriate to report our experience. Because of effective medical therapy of acid peptic disease, patients who formerly required conduit replacement may now be candidates for revision; however, the medical literature does not specify when conduit revision, as opposed to conduit replacement, is indicated; also, no guidance is provided regarding what constitutes effective operative revision. Innovative techniques that stretch and elongate the atretic esophagus will likely lessen the use of conduits in esophageal atresia; nevertheless, colon conduits are useful in many other clinical situations and will remain an essential part of the armamentarium of pediatric, general, and thoracic surgeons. This report highlights the DeMeester and Tannuri technique, whereby a colon conduit is prepared like a Roux limb. The mesentery is divided only once; the conduit's blood supply is not severed from the distal mesocolon. This innovation improves a conduit's blood supply and lessens its attendant complications. Lastly, we describe a muscle splitting, posterolateral thoracotomy technique that is simpler than the alternatives and is useful in a variety of clinical situations.
Assuntos
Colo/transplante , Atresia Esofágica/cirurgia , Estenose Esofágica/cirurgia , Anastomose Cirúrgica , Criança , Estenose Esofágica/etiologia , Seguimentos , Humanos , Masculino , Complicações Pós-Operatórias , Reoperação , Estômago/cirurgia , Fatores de Tempo , Transplante AutólogoRESUMO
BACKGROUND/PURPOSE: Previous reports indicate that complete resection of high-risk neuroblastoma improves outcome but may entail high surgical complication rates. The authors evaluated the effect of complete primary site resection on event-free survival (EFS), overall survival (OS), and complication rates in patients entered on a high-risk neuroblastoma treatment protocol. METHODS: A total of 539 eligible patients with high-risk neuroblastoma were entered on protocol CCG-3891. Patients were assigned randomly to continuation chemotherapy or autologous bone marrow transplantation. Surgical resection was performed at diagnosis or after induction chemotherapy. Surgeons assessed resection as complete (CR), minimal residual (<5%, MR), or partial (PR). Incomplete resections received secondary resection or 10 Gy of external beam radiation. Patients were evaluated for EFS, OS, and complications of surgery based on completeness of overall best resection. RESULTS: The proportion of patients resectable at diagnosis was 27% for CR and 14% for MR. This improved after chemotherapy to 45% and 25%. Complication rates based on completeness of resection were 29%, 38%, and 36% for CR, MR, and PR, respectively. Estimated 5-year EFS rate was 30% +/- 3% for patients who achieved CR (n = 210) compared with 25% +/- 3% (P =.1010) for those with less than CR (n = 258). CONCLUSIONS: Resectability improved after neoadjuvant chemotherapy. Complete resection did not increase complications. There was a small survival benefit for complete resection. This study suggests that complete resection may still be important in the current era of intense chemotherapy and transplant.
Assuntos
Neuroblastoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Feminino , Amplificação de Genes , Genes myc , Humanos , Lactente , Tábuas de Vida , Masculino , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasia Residual , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Neuroblastoma/radioterapia , Radioterapia Adjuvante , Indução de Remissão , Fatores de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
CBPFM is a rare finding associated with GERD in infancy. To our knowledge this case represents the twenty-fifth reported case in a child and the one-hundred and thirty first reported case in the literature overall. This case serves to remind the practitioner that children with symptoms of GER may not be just one of the endless number of happy spitters.